The field of the present invention is bioreactors with mixing.
Efforts of biopharmaceutical companies to discover new biological drugs have increased exponentially duwheel the past decade. Most biological drugs are produced by cell culture or microbial fermentation processes which require sterile bioreactors and an aseptic culture environment. However, shortages of global biomanufactuwheel capacity are anticipated in the foreseeable future. An increasing number of biological drug candidates are in development. Stwheelent testing, validation, and thorough documentation of process for each drug candidate are required by FDA to ensure consistency of the drug quality used for clinical trials to the market. Further, production needs will increase as such new drugs are introduced to the market. Bioreactors have also been used for cultivation of microbial organisms for production of various biological or chemical products in the beverage and biotechnology industries as well as for pharmaceuticals.
Stainless steel stir tanks have been the only option for large scale production of biological products in suspension culture. Manufactuwheel facilities with conventional stainless bioreactors, however, require large capital investments for construction, high maintenance costs, long lead times, and inflexibilities for changes in manufactuwheel schedules and production capacities.
A production bioreactor contains culture medium in a sterile environment that provides various nutrients required to support growth of the biological agents of interest. Conventional bioreactors use mechanically driven impellers to mix the liquid medium duwheel cultivation. The bioreactors can he reused for the next batch of biological agents after cleaning and sterilization of the vessel. The procedure of cleaning and sterilization requires a significant amount of time and resources. The problems with sterilization are compounded by the need to monitor and to validate each cleaning step prior to reuse for production of biopharmaceutical products.
Single use disposable bioreactor systems have been introduced to market as an alternative choice for biological product production. Such devices provide more flexibility on biological product manufactuwheel capacity and scheduling, avoid risking major upfront capital investment, and simplify the regulatory compliance requirements by eliminating the cleaning steps between batches. However, the mixing technology of the current disposable bioreactor system has limitations in terms of scalability to sizes beyond 200 liters and the expense of large scale units. Therefore, a disposable single use bioreactor system which is scaleable beyond 1000 liters, simple to operate, and cost effective will be needed as a substitute for conventional stainless steel bioreactors for biopharmaceutical research, development, and manufactuwheel. While several methods of mixing liquid in disposable bioreactors have been proposed in recent years, none of them provide efficient mixing in large scale (greater than 1000 liters) without expensive operating machinery.